The invention relates to compositions for reducing post-prandial blood glucose in humans and, more specifically, to a proteinase inhibitor that delays gastric emptying and reduces post-prandial glycemia which may be beneficial in combating obesity and Type II diabetes.
Regulation of body weight depends on genetic as well as physiologic and lifestyle factors that are known to influence energy balance, such as diet, appetite control, metabolism, and physical activity (Aronne, L. J. (2001) J Clin Psychiatry 62, 13-22; Fernandez-Lopez, J. A., Remesar, X., Foz, M. & Alemany, M. (2002) Drugs 62, 915-44). Despite measures to combat obesity and an increased awareness of the associated co-morbidities, the condition has become an epidemic, with nearly 60% of Americans classified as overweight or obese (Visscher, T. L. & Seidell, J. C. (2001) Annu Rev Public Health 22, 355-75). Since the gene pool has not changed, researchers believe the culprit is primarily due to a combination of environmental and lifestyle influences. A focus on dietary fat as a leading cause of obesity the last several decades has been successful in reducing overall fat intake by Americans (from 40% to just over 30% of total calories, from the 1960's to present), but has done little to stave the rise in obesity rates (Lichtenstein, A. H., Kennedy, E., Barrier, P., Danford, D., Ernst, N. D., Grundy, S. M., Leveille, G. A., Van Horn, L., Williams, C. L. & Booth, S. L. (1998) Nutr Rev 56, S3-19; discussion S19-28).
Corresponding with this profound rise in obesity incidence, a similar rise in the consumption of foods higher in processed and refined carbohydrates has been observed (Grundy, S. M. (1998) Am J Clin Nutr 67, 563S-72S), along with an increased incidence of type II diabetes (Disdier-Flores, O. M., Rodriguez-Lugo, L. A., Perez-Perdomo, R. & Perez-Cardona, C. M. (2001) P R Health Sci J 20, 123-30; Felber, J. P. & Golay, A. (2002) Int J Obes Relat Metab Disord 26 Suppl 2, S39-45). These events have led researchers to question the effect of dietary fat on body fat accumulation, and suggest that dietary factors other than fat consumption play an important role in body weight regulation (Willett, W. C. (1998) Am J Clin Nutr 67, 556S-562S; Willett, W. C. (2002) Obes Rev 3, 59-68). Evidence now exists suggesting that chronic glycemia can lead to increased fat synthesis and storage, and may contribute significantly to the development of obesity and other chronic diseases such as diabetes and cardiovascular disease (Jenkins, D. J., Kendall, C. W., Augustin, L. S., Franceschi, S., Hamidi, M., Marchie, A., Jenkins, A. L. & Axelsen, M. (2002) Am J Clin Nutr 76, 266S-73S; Ludwig, D. S. (2002) JAMA 287, 2414-23; Leeds, A. R. (2002) Am J Clin Nutr 76, 286S-9S). Concerns over safety and efficacy of many anti-obesity products have limited their usefulness. Therefore, developments of natural, safe, and effective nutraceutical and/or medications that can help treat or prevent obesity are essential to mitigate this public health crisis.
Both soybeans and potatoes are sources of proteinase inhibitors (PI's), proteins that have been hypothesized to enhance the release of cholecystokinin (CCK), one of several gut peptides that regulate gastric emptying and satiety in humans (Liddle, R. A. (1995) Am J Physiol 269, G319-27; Beglinger, C. (1994) Ann N YAcad Sci 713, 219-25; Beglinger, C. (2002) Curr Opin Investig Drugs 3, 587-8). Delayed gastric emptying, in turn, has been shown to result in a decreased rate of glucose absorption, and lower post-prandial glucose levels (Lefebvre, P. J. & Scheen, A. J. (1999) Eur J Clin Invest 29 Suppl 2, 1-6). Proteinase inhibitor II (PI2) is a naturally occurring 21 kDa dimer and potent trypsin and chymotrypsin inhibitor present in white potatoes (Melville, J. C. & Ryan, C. A. (1972) J Biol Chem 247, 3445-53; Bryant, J., Green, T. R., Gurusaddaiah, T. & Ryan, C. A. (1976) Biochemistry 15, 3418-24). Previous studies using large doses of highly pure PI2 demonstrated increased CCK release and satiety in humans (Peikin, S. R., Springer, C. J., Dockray, G. J., Blundell, J. E., Hill, A. J., Calam, J. & Ryan, C. A. (1987) Gastroenterology 92, A1570; Hill, A. J., Peikin, S. R., Ryan, C. A. & Blundell, J. E. (1990) Physiol Behav 48, 241-6; Schwartz, J. G., Guan, D., Green, G. M. & Phillips, W. T. (1994) Diabetes Care 17, 255-62). In addition, oral administration of PI2 at high doses in a liquid form has been shown to reduce both post-prandial glucose and insulin levels in humans (Schwartz, et al., supra), supporting the use of PI2 as both a promising hunger management tool and an effective agent to reduce post-prandial glycemia experienced by the body.
The development of an efficient proprietary commercial process providing an extract from potatoes containing PI2 has increased the availability of this compound. It was hypothesized that administration of PI2 extract as a nutraccutical ingredient in a low dose, encapsulated form, prior to a meal, might reduce post-prandial glucose levels. This could have important implications for the use of PI2 as part of a diet to help maintain healthy blood sugar levels and reduce the propensity for weight gain.